TGS-GapCloser: A fast and accurate gap closer for large genomes with low coverage of error-prone long reads.
Gigascience, 2020/09/01;9(9)
Xu M[1, 2, 3], Guo L[1, 4], Gu S[1, 4], Wang O[3, 5], Zhang R[1], Peters BA[3, 6], Fan G[1, 3], Liu X[1, 2, 3, 7], Xu X[3, 7], Deng L[1, 2, 3], Zhang Y[3, 6]
Affiliations
PMID: 32893860DOI: 10.1093/gigascience/giaa094
Impact factor: 7.658
Abstract
background: Analyses that use genome assemblies are critically affected by the contiguity, completeness, and accuracy of those assemblies. In recent years single-molecule sequencing techniques generating long-read information have become available and enabled substantial improvement in contig length and genome completeness, especially for large genomes (>100 Mb), although bioinformatic tools for these applications are still limited.
findings: We developed a software tool to close sequence gaps in genome assemblies, TGS-GapCloser, that uses low-depth (∼10×) long single-molecule reads. The algorithm extracts reads that bridge gap regions between 2 contigs within a scaffold, error corrects only the candidate reads, and assigns the best sequence data to each gap. As a demonstration, we used TGS-GapCloser to improve the scaftig NG50 value of 3 human genome assemblies by 24-fold on average with only ∼10× coverage of Oxford Nanopore or Pacific Biosciences reads, covering with sequence data up to 94.8% gaps with 97.7% positive predictive value. These improved assemblies achieve 99.998% (Q46) single-base accuracy with final inserted sequences having 99.97% (Q35) accuracy, despite the high raw error rate of single-molecule reads, enabling high-quality downstream analyses, including up to a 31-fold increase in the scaftig NGA50 and up to 13.1% more complete BUSCO genes. Additionally, we show that even in ultra-large genome assemblies, such as the ginkgo (∼12 Gb), TGS-GapCloser can cover 71.6% of gaps with sequence data.
conclusions: TGS-GapCloser can close gaps in large genome assemblies using raw long reads quickly and cost-effectively. The final assemblies generated by TGS-GapCloser have improved contiguity and completeness while maintaining high accuracy. The software is available at https://github.com/BGI-Qingdao/TGS-GapCloser.
Keywords: MHC; gap closure; genome assembly; ginkgo; third-generation sequencing
MeSH terms
Computational Biology; Genome, Human; High-Throughput Nucleotide Sequencing; Humans; Sequence Analysis, DNA; Software
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